Grant Award Details
Grant Application Details
- AAV Gene Therapy for Treating Congenital Hereditary Endothelial Dystrophy associated with Biallelic SLC4A11 Mutations
Therapeutic candidate rAAV8-EF1α-hSLC4A11 is a recombinant AAV vector with single-stranded cDNA encoding the wild-type human SLC4A11 protein.
Area of Impact
The candidate is for treatment of congenital hereditary endothelial dystrophy, an orphan disease associated with congenital corneal opacification.
Mechanism of Action
Therapeutic candidate rAAV8-EF1α-hSLC4A11 introduces normal copies of human SLC4A11 gene into the diseased corneal endothelial cells to compensate for loss of function pathologic biallelic SLC4A11 gene mutations, thus restoring the production of the defective or missing SLC4A11 protein and reverting the disease phenotype.
Unmet Medical Need
Corneal transplantation is the only treatment for children with CHED. However, pediatric corneal transplantation is associated with an increased risk of intraoperative and postoperative complications, including higher rates of transplant rejection and failure.
Major Proposed Activities
- Studies in Mouse Disease Model to Determine Dose and Dose Schedule Optimization
- Manufacturing of GMP-like Candidate for Pilot Safety Studies
- Early Safety and Toxicology Studies in Rabbits
If successful, this project will be the first AAV gene therapy for an anterior segment disorder entering a Phase I clinical trial and will demonstrate CIRM’s and FNIH’s commitment to supporting gene therapy trials for blinding pediatric anterior segment disorders that affect children in California and globally. Experience obtained via this project, in which the CDMO is California-based, will accelerate future efforts to make cell and gene therapies available to the people of California.